Scientists demonstrate new technique to help understand how cells develop and function

27 April 2012

Scientists at Cambridge University and the Babraham Institute, which receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC), have demonstrated a new technique that will significantly improve scientists' ability to perform epigenetics research and help unlock the door to understanding how cells develop and function. Epigenetics is a branch of genetics that studies modifications to the DNA which affect gene activity. The research, published in the journal Science has important implications for stem cell research and the development of regenerative medicines.

All the cells in the body have the same DNA sequence (genome), but it is how this DNA sequence is interpreted that results in the formation of different cell types. Epigenetic changes control how a DNA sequence is interpreted, specifically how different genes are switched on and off in different cell types, tissues and organs.

One of the most studied epigenetic marks is the addition of a very small chemical modification called a methyl group to DNA, which turns associated genes off. Methyl groups are always added to the DNA base cytosine and so this chemical modification is called 5-methylcytosine (5mC). Babraham Institute scientists are involved in researching the role of another DNA chemical modification in mammals called 5-hydroxymethyl-cytosine (5hmC), which is believed to be important for stem cell function, helping to define how the body develops. 5hmC may be a separate epigenetic mark or possibly be part of the process which removes methyl groups from DNA, allowing genes to be switched on again. Decoding the 'epigenome' will provide greater understanding of how cells are regulated and has major implications for regenerative medicine and how cells such as stem cells can be controlled.

Professor Shankar Balasubramanian FRS, of the University of Cambridge Chemistry Department and Cancer Research UK Cambridge Research Institute, and his PhD student Michael Booth invented new chemistry to allow the recently discovered base 5hmC to be sequenced in DNA at single base resolution. This was not possible using existing methods. In a fruitful collaboration between the Cambridge group (led by Balasubramanian) and the Babraham Institute (led by Professor Wolf Reik FRS), this method was applied to sequence 5hmC and 5mC in embryonic stem cell genomic DNA.

Balasubramanian, whose group previously co-invented Solexa sequencing, explained, "Sequencing DNA is becoming an increasingly important part of science and medicine and we are pleased to have met the challenge of finding a way to sequence this important new base modification."

Professor Wolf Reik who led the study at the Babraham Institute said, "It has recently become apparent that in addition to DNA methylation, there are other modifications of DNA, such as for example hydroxymethylation. This suggests that DNA modifications are more dynamic than we previously thought. With the new method we are now in a position to map these modifications at great precision, and to relate them to stem cell function, ageing, and perhaps more generally to how the environment interacts with the genome."

This research was also supported by the Medical Research Council, the Wellcome Trust and the EU.